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Pharmacokinetics and disposition of flupirtine in the horse
Full text linkFlupirtine (FLU) is a non-opioid analgesic drug, with no antipyretic or anti-inflammatory effects, used in the treatment of a wide range of pain states in human beings. It does not induce the side effects associated with the classical drugs used as pain relievers. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy horses. Six mixed breed adult mares were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, paired, cross-over design (2 × 2 Latin-square). Group 1 (n = 3) received a single dose of 1 mg/kg of FLU injected IV into the jugular vein. Group 2 (n = 3) received FLU (5 mg/kg) via nasogastric tube. The animals then swapped groups after a 1-week wash-out period and the doses were repeated. Blood samples (5 mL) were collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36 and 48 h and plasma was then analysed by a validated HPLC method.Some mild and transient adverse effects (that spontaneously resolved within 5 min) were observed in 2/6 animals after IV administration. No adverse effects were noticed in the PO administration group. After IV and PO administrations, FLU was detectable in plasma for up to 36 h. The mean elimination half-life was longer after PO (10.27 h) than after IV (3.02 h) administration. The oral bioavailability was 71.4 ± 33.1%. After compartmental simulation/modelling, an oral dose of 2.6 mg/kg was calculated to give C and AUC values in horses similar to those reported in humans after a clinical dose administration with a theoretical FLU effective plasma concentration of 187 ng/mL. These findings may form the basis for further studies concerning this active ingredient in equine medicine
Pharmacokinetic/pharmacodynamic evaluation of grapiprant in a carrageenan-induced inflammatory pain model in the rabbit
No full textGrapiprant is the novel selective EP4 receptor inhibitor recently issued on the veterinary market for dogs affected by osteoarthritis. The aim of this study was twofold: to evaluate the pharmacokinetics and the pharmacodynamics of grapiprant in the induced inflammatory pain model in the rabbit after a single IV injection of 2 mg/kg; to compare the thermal antinociception effect after 2 mg/kg IV grapiprant, with that generated by 0.5 mg/kg meloxicam SC injected. Rabbits (n = 12) were randomly assigned to two crossover studies (single-dose, two-period crossover). The first study group A (n = 3) received a single IV dose of grapiprant at 2 mg/kg dissolved in ethanol. Group B (n = 3) received a single IV injection of ethanol (equivalent volume to grapiprant volume) at the same site. The second study group C (n = 3) received a single SC dose of meloxicam at 0.5 mg/kg. Group D (n = 3) received a single SC injection of 15% ethanol (equivalent volume to grapiprant volume) at the same site. After a 2-week washout period, the groups were rotated and the experiments repeated. Blood samples (0.7 mL) were collected from the right ear artery at assigned times and grapiprant plasma concentrations determined by a validated HPLC-FL method. Three hours prior to administration of the drugs, inflammation was induced by SC injection of lambda carrageenan (200 μL, 3% in physiological saline) under the plantar surface of the right hind paw. At a similar time to the blood collection, an infrared thermal stimuli (40 °C) was applied to the plantar surface of the rabbits' hindlimbs to evaluate the thermal withdrawal latency (TWL). The thermal antinociceptive effect was expressed as maximum possible response (% MPR). Grapiprant plasma concentrations were detectable up to the 10-h time point (concentration range 17-7495 ng/mL). The grapiprant-treated group showed a significant increase in TWL from 1 h and up to 10 h after drug administration compared to the control. In contrast, the meloxicam group showed a significant increase in TWL from 4 up to 10 h after drug administration, compared to control. The maximal MPR% was not statistically different between the grapiprant and meloxicam group from 4 to 8 h, while significant differences were shown at 1, 1.5, 2, 10 and 24 h. Given these findings, grapiprant appears to be an attractive option for antinociception in rabbits, due to its rapid onset and extended duration of effect
Flupirtine: pharmacokinetics and disposition in the horse
No full textNTRODUCTION
Flupirtine (FLU) is a non-opioid analgesic drug with no antipyretic
or antiphlogistic effects, it is used in the treatment of a
wide range of pain states in human beings. It does not induce
the side effects associated with the classical drugs used as pain
relievers. The aim of this study was to evaluate the pharmacokinetic
profiles of FLU after IV and PO administration in
healthy horses.
MATERIALS AND METHODS
Six mixed breed adult mares (aged 9 to 13 years and weighing
480 to 590 kg) were randomly assigned to two treatment
groups using an open, single-dose, two-treatment, two-phase,
paired, cross-over design (2 9 2 Latin-square). The Animal
Welfare Committee of the University of Pisa, approved the
study. Group 1 (n = 3) received a single dose of 1 mg kg
1 of
FLU injected IV into the jugular vein. Group 2 (n = 3) received
FLU (5 mg kg
1) via nasogastric tube. The wash out period
was 1-week. Blood samples (5 ml) were collected at 0.25, 0.5,
0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36 and 48 h and plasma was
then analysed by a validated HPLC method. Pharmacokinetic
curves were fit according to a compartmental analysis by Win-
Nonlin (V5.3.1).
RESULTS AND CONCLUSIONS
Some mild and transient adverse effects (that spontaneously
resolved within 5 min) were observed in 2 out of 6 animals
after IV administration. No adverse effects were noticed in the
PO administration group. A bi-compartmental model best fitted
the plasma concentrations after IV and PO administrations in
all the six horses. After IV and PO administrations, FLU was
detectable in plasma for up to 36 h. The mean elimination
half-life was longer after PO (10.27 h) than after IV (3.02 h)
administration. The oral bioavailability was about 70%. This
higher than that reported in cats [1] and dogs [2]. After in silico
pharmacokinetic simulation/modelling, an oral dose of
2.6 mg kg
1 in horses has been calculated to give Cmax and
AUC values similar to those reported in humans after a clinical
dose administration [3] with a theoretical FLU effective plasma
concentration of 187 ng ml
1. The average oral pharmacokinetic
profile indicated that this value is exceeded for over 9
and 15 h following administration of 2.6 and 5 mg kg
1 of
FLU, respectively. This study could pave the road for further
study about the use of this active ingredient in equine medicine.INTRODUCTION Flupirtine (FLU) is a non-opioid analgesic drug with no antipyretic or antiphlogistic effects, it is used in the treatment of a wide range of pain states in human beings. It does not induce the side effects associated with the classical drugs used as pain relievers. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy horses. MATERIALS AND METHODS Six mixed breed adult mares (aged 9 to 13 years and weighing 480 to 590 kg) were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, paired, cross-over design (2 9 2 Latin-square). The Animal Welfare Committee of the University of Pisa, approved the study. Group 1 (n = 3) received a single dose of 1 mg kg 1 of FLU injected IV into the jugular vein. Group 2 (n = 3) received FLU (5 mg kg 1) via nasogastric tube. The wash out period was 1-week. Blood samples (5 ml) were collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36 and 48 h and plasma was then analysed by a validated HPLC method. Pharmacokinetic curves were fit according to a compartmental analysis by Win- Nonlin (V5.3.1). RESULTS AND CONCLUSIONS Some mild and transient adverse effects (that spontaneously resolved within 5 min) were observed in 2 out of 6 animals after IV administration. No adverse effects were noticed in the PO administration group. A bi-compartmental model best fitted the plasma concentrations after IV and PO administrations in all the six horses. After IV and PO administrations, FLU was detectable in plasma for up to 36 h. The mean elimination half-life was longer after PO (10.27 h) than after IV (3.02 h) administration. The oral bioavailability was about 70%. This higher than that reported in cats [1] and dogs [2]. After in silico pharmacokinetic simulation/modelling, an oral dose of 2.6 mg kg 1 in horses has been calculated to give Cmax and AUC values similar to those reported in humans after a clinical dose administration [3] with a theoretical FLU effective plasma concentration of 187 ng ml 1. The average oral pharmacokinetic profile indicated that this value is exceeded for over 9 and 15 h following administration of 2.6 and 5 mg kg 1 of FLU, respectively. This study could pave the road for further study about the use of this active ingredient in equine medicine
Pharmacokinetic profiles of the active metamizole metabolites in healthy horses
Full text linkMetamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among other secondary metabolites, 4-aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 9 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC-UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0-last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0-last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54.
This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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